We propose to investigate genes of human cells that are potentially capable of inducing oncogenic transformation. Transforming genes of normal human cells will be identified by transfection of NIH 3T3 mouse cells with DNA fragments of normal diploid human embryo fibroblasts. Molecular clone activated transforming genes will be isolated from DNAs of NIH cells transformed by human DNA fragments. The organization and biological activity of human and mouse DNA sequences in the cloned transforming genes will be investigated and the extent of transcription of transforming gene sequences in normal and DNA-transformed cells will be compared. Transforming genes cloned from human DNA-transformed NIH cells will be used to estimate the number of potential endogenous transforming genes in human DNA and to clone homologous genes from normal human cells. The role of flanking cellular DNA sequences in regulation of potential endogenous transforming genes cloned from normal cell DNA will be studied. The transcription, organization and biological activity of endogenous transforming genes in transformed human cell lines and in naturally-occurring human tumors will be investigated.